The objectives of the proposed research are to examine several thiono-sulfur-containing compounds for toxic effects upon the hepatic systems responsible for transport of organic anions, cations and neutral compounds into the bile; to determine the hepatic site at which thiono-sulfur-containing compounds are exerting toxicity on hepatic transport; and to examine the effects of thiono-sulfur-containing compounds on bile flow and constituents of bile. The objectives will be accomplished by administering the thiono-sulfur-containing compounds to rats and after an appropriate time interval administering dibromosulfobromophthalein, sulfobromophthalein, procaineamide ethobromide or ouabain and determining their plasma disappearance, biliary excretion, and liver concentration. At the same time, the effect of the thiono-sulfur-containing compounds on bile flow and bile constituents will be determined. The results obtained from treated rats will be compared with results obtained from untreated rats. The effect of thiono-sulfur-containing compounds on isolated parenchymal cell uptake of organic anions, cations and neutral compounds; and the effect of thiono-sulfur-containing compounds on ligandin will be examined as possible sites of toxic action.